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Generation Genome: Sequencing in the NHS

Genomics is not tomorrow. Its here today. I believe genomic services should be available to more patients, whilst being a cost-effective service in the NHS. This is exciting science with the potential for fantastic improvements in prevention, health protection and patient outcomes.  Now we need to welcome the genomic era and deliver the genomic dream!”      

– Professor Dame Sally Davies, Annual Report of the Chief Medical Office, 2016: Generation Genome


Today the Chief Medical Officer (CMO) in England, Professor Dame Sally Davies, has published her annual report on health in England with a specific focus on genomics.

This particular report, entitled “Generation Genome, looks in detail at the issues surrounding the use of next generation sequencing (NGS) to characterise patient genomes and how it could, and more importantly should, be utilised within the NHS in order to guide and develop patient care.

Crucially, from the view point of Precision-Panc, the report not only addresses NGS in terms of the needs of patients affected by rare diseases, but also considers the needs of patients affected by cancer.

In Generation Genome, Chapter five lead and author, Dr. Ultan McDermott, predicts that NGS technology “has the potential for huge cost-savings in the treatment of cancer patients, by building knowledge banks of clinical outcome“ and that “NGS assays will allow a single test to detect a large range of events, saving time, money and precious tissue material but at the expense of requiring increasingly complex informatics requirements“.

Professor Andrew Biankin, Regius Professor of Surgery at the University of Glasgow and Chief Investigator for Precision-Panc, responded positively to the document whilst noting that adjusting health care systems to enable the delivery of precision medicine will enhance research, innovation, treatment development and investment in the U.K.

Through the efforts of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), amongst others, the cancer research community has previously identified many of the cancer genes and associated chromosomal defects involved in the development of a broad range of cancers.

It is true to say that we now have more information than ever before about the range of subtypes of cancer, their behaviours and associated survival rates in addition to potential treatment options/responses.  Through such large-scale studies, it has become apparent that every cancer is slightly different to the next…even when cancer arises from the same tissue in different patients.

We have now entered the genomic era and have unprecedented opportunities to examine and correlate cancer genomes to clinical outcomes. This is the main goal of Precision-Panc, and also of ICGCmed (ICGC for Medicine which builds on the foundation of ICGC studies), to identify why patients respond to treatment or not.

Our own research to date confirms that bringing genomic analyses into play for the treatment of pancreatic cancers would be a game changer for our patients.  Professor Biankin feels that the diversity of drug targets in pancreatic cancer is a likely reason why we have made little progress. A precision oncology approach offers significant opportunities to shift the needle for this recalcitrant cancer.

We already know that there are different subtypes of pancreatic cancer.  Our research published in Nature in 2016, based upon the work of the Glasgow Precision Oncology Laboratory at the University of Glasgow and the Australian Pancreatic Genome Initiative, confirmed that that there are four main subtypes of pancreatic cancer that behave slightly differently from each other.

Further research led by Italian colleagues from ARC-Net & University and Hospital Trust of Verona, and including those researchers mentioned previously at Glasgow and APGI, outlined the landscape of pancreatic neuroendocrine tumours (PNETs).  This specific, and rare, subtype of pancreatic tumour develops from the cells that are responsible for the production of hormones, such insulin, that help to control blood sugar levels in the body. In general, PNETs can be classified as either slow-growing or aggressive.  It is not possible to know which characteristic a PNET has until it is classified at a molecular level.

We know that more than 90% of cancers are caused by gene changes that happen during normal day-to-day living – for example, aging, smoking, and sedentary lifestyles.  This report also discusses the use of risk-stratified cancer screening strategies which could be more effective if they identify patients most likely to benefit, and least likely to be harmed, by such an approach (chapter 10).  By combining patient’s genetic risks with other risk factors, such as smoking, the efficiency of screening can be improved.

Further assessment of the cost-effectiveness, accessibility and feasibility of risk-stratified cancer screening, alongside the requirement for information exchange with the public and health care worker training required to implement it, requires further detailed evaluation. The chapter authors also note that the key to the implementation is a concerted and joint multi-disciplinary approach. In the first instance, such an approach would be unlikely to benefit pancreatic patients but would benefit those affected by breast, colorectal, prostate and lung cancer.

There are significant challenges to bring NGS into the clinic, and producing the sequence data is arguably the simplest step in the process.  Obtaining tissues from which DNA can be extracted is a major challenge – especially for pancreatic cancer patients. Changing the processes and procedures that have been used for decades is no simple task but it is possible.  We have been working on the protocols and processes that utilise endoscopic ultrasound (EUS) biopsies to obtain small amounts of material for genome and panel sequencing approaches for pancreatic cancer. Our colleagues at Glasgow Royal Infirmary have been engaged and proactive in eliciting a change in the patient pathway to successfully enable this.

The sheer amount of data that could be generated by bringing NGS into the clinic as proposed in this document will mean that we have to rethink the strategies for storage and processing of that data. And not just genomic data – other ‘omic data in addition to more detailed information about the patient’s health history will be essential to facilitate an accurate interpretation of the patient genome under study.

In chapter 13, the problem is summarised thus: “Genomic datasets are big. Genomics England’s systems, designed to process 100,000 genomes, has 16 petabytes of storage (= 16,000 terabytes). Compare this with NHS Digital’s systems which process millions of transactions but hold data only in the low 100s of terabytes.

The authors therefore sensibly note that a central repository with a significant High Performance Compute environment will be required alongside standardised analytical tools and pipelines.   In addition, health informatics, bioinformatics and data science skills will have to be developed and nurtured within the NHS workforce in order to effectively manage and interpret genomic data. Further issues around patient consent and data sharing are also discussed in detail.

In short, we understand that it is possible to map the changes in a cancer genome in order to begin to think about how that cancer could be treated most effectively.   Reading this document, and thinking about our own research to date, we are encouraged by the proposal to bring NGS into the clinic within 5 years.   However, we know that its implementation will require careful thought, realistic planning and, most importantly, engagement and education of both clinicians and patients.  We are cautiously optimistic that genome sequencing of cancer patients is on the horizon.  

Therefore, closer to home, we hope that the launch of Precision-Panc trials later this year will enable pancreatic cancer patients to access molecular phenotyping to guide their own individual patient journey down a longer, and much more positive track than has been previously possible.  

We give thanks to the patients and their families that have engaged with forward thinking clinical researchers and participated in the studies that have led to the conclusion that genome sequencing can make a difference. Without those patients, who have been willing to donate samples without any promised personal benefit, this conversation wouldn’t be taking place.